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| PMID |
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| TITLE |
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| Genome-wide association study of blood lead shows multiple associations near ALAD. |
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| ABSTRACT |
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| Exposure to high levels of environmental lead, or biomarker evidence of high body lead content, is associated with anaemia, developmental and neurological deficits in children, and increased mortality in adults. Adverse effects of lead still occur despite substantial reduction in environmental exposure. There is genetic variation between individuals in blood lead concentration but the polymorphisms contributing to this have not been defined. We measured blood or erythrocyte lead content, and carried out genome-wide association analysis, on population-based cohorts of adult volunteers from Australia and UK (N = 5433). Samples from Australia were collected in two studies, in 1993-1996 and 2002-2005 and from UK in 1991-1992. One locus, at ALAD on chromosome 9, showed consistent association with blood lead across countries and evidence for multiple independent allelic effects. The most significant single nucleotide polymorphism (SNP), rs1805313 (P = 3.91 × 10(-14) for lead concentration in a meta-analysis of all data), is known to have effects on ALAD expression in blood cells but other SNPs affecting ALAD expression did not affect blood lead. Variants at 12 other loci, including ABO, showed suggestive associations (5 × 10(-6) > P > 5 × 10(-8)). Identification of genetic polymorphisms affecting blood lead reinforces the view that genetic factors, as well as environmental ones, are important in determining blood lead levels. The ways in which ALAD variation affects lead uptake or distribution are still to be determined. |
| © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com. |
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| DATE PUBLISHED |
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| HISTORY |
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| PUBSTATUS |
PUBSTATUSDATE |
| received |
2014/11/16 |
| accepted |
2015/03/24 |
| aheadofprint |
2015/03/27 |
| entrez |
2015/03/31 06:00 |
| pubmed |
2015/03/31 06:00 |
| medline |
2015/03/31 06:00 |
| pmc-release |
2016/07/01 00:00 |
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| AUTHORS |
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| NAME |
COLLECTIVENAME |
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
| Warrington NM |
|
Warrington |
Nicole M |
NM |
|
University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Australia. |
| Zhu G |
|
Zhu |
Gu |
G |
|
QIMR Berghofer Medical Research Institute, Locked Bag 2000, Royal Brisbane Hospital, Queensland 4029, Australia. |
| Dy V |
|
Dy |
Veronica |
V |
|
Royal Prince Alfred Hospital, Sydney, Australia. |
| Heath AC |
|
Heath |
Andrew C |
AC |
|
Department of Psychiatry, Washington University School of Medicine, St Louis, MO, USA. |
| Madden PA |
|
Madden |
Pamela A F |
PA |
|
Department of Psychiatry, Washington University School of Medicine, St Louis, MO, USA. |
| Hemani G |
|
Hemani |
Gibran |
G |
|
MRC Integrative Epidemiology Unit, School of Social and Community Medicine and. |
| Kemp JP |
|
Kemp |
John P |
JP |
|
University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Australia, MRC Integrative Epidemiology Unit, School of Social and Community Medicine and. |
| Mcmahon G |
|
Mcmahon |
George |
G |
|
MRC Integrative Epidemiology Unit, School of Social and Community Medicine and. |
| St Pourcain B |
|
St Pourcain |
Beate |
B |
|
School of Social and Community Medicine and. |
| Timpson NJ |
|
Timpson |
Nicholas J |
NJ |
|
MRC Integrative Epidemiology Unit, School of Social and Community Medicine and. |
| Taylor CM |
|
Taylor |
Caroline M |
CM |
|
Centre for Child and Adolescent Health, School of Social and Community Medicine, University of Bristol, Bristol, UK. |
| Golding J |
|
Golding |
Jean |
J |
|
School of Social and Community Medicine and. |
| Lawlor DA |
|
Lawlor |
Debbie A |
DA |
|
MRC Integrative Epidemiology Unit, School of Social and Community Medicine and. |
| Steer C |
|
Steer |
Colin |
C |
|
Centre for Child and Adolescent Health, School of Social and Community Medicine, University of Bristol, Bristol, UK. |
| Montgomery GW |
|
Montgomery |
Grant W |
GW |
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QIMR Berghofer Medical Research Institute, Locked Bag 2000, Royal Brisbane Hospital, Queensland 4029, Australia. |
| Martin NG |
|
Martin |
Nicholas G |
NG |
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QIMR Berghofer Medical Research Institute, Locked Bag 2000, Royal Brisbane Hospital, Queensland 4029, Australia. |
| Davey Smith G |
|
Davey Smith |
George |
G |
|
MRC Integrative Epidemiology Unit, School of Social and Community Medicine and. |
| Evans DM |
|
Evans |
David M |
DM |
|
University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Australia, MRC Integrative Epidemiology Unit, School of Social and Community Medicine and. |
| Whitfield JB |
|
Whitfield |
John B |
JB |
|
QIMR Berghofer Medical Research Institute, Locked Bag 2000, Royal Brisbane Hospital, Queensland 4029, Australia, John.Whitfield@qimrberghofer.edu.au. |
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| INVESTIGATORS |
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| JOURNAL |
|
| VOLUME: 24 |
| ISSUE: 13 |
| TITLE: Human molecular genetics |
| ISOABBREVIATION: Hum. Mol. Genet. |
| YEAR: 2015 |
| MONTH: Jul |
| DAY: 1 |
| MEDLINEDATE: |
| SEASON: |
| CITEDMEDIUM: Internet |
| ISSN: 1460-2083 |
| ISSNTYPE: Electronic |
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| MEDLINE JOURNAL |
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| MEDLINETA: Hum Mol Genet |
| COUNTRY: England |
| ISSNLINKING: 0964-6906 |
| NLMUNIQUEID: 9208958 |
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| PUBLICATION TYPE |
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| PUBLICATIONTYPE TEXT |
| Journal Article |
| Research Support, N.I.H., Extramural |
| Research Support, Non-U.S. Gov't |
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| COMMENTS AND CORRECTIONS |
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| REFTYPE |
REFSOURCE |
REFPMID |
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| GRANTS |
|
| GRANTID |
AGENCY |
COUNTRY |
| AA007535 |
NIAAA NIH HHS |
United States |
| AA013320 |
NIAAA NIH HHS |
United States |
| AA013321 |
NIAAA NIH HHS |
United States |
| AA013326 |
NIAAA NIH HHS |
United States |
| AA014041 |
NIAAA NIH HHS |
United States |
| DA012854 |
NIDA NIH HHS |
United States |
| MC_PC_15018 |
Medical Research Council |
United Kingdom |
| MC_UU_12013/1 |
Medical Research Council |
United Kingdom |
| MC_UU_12013/3 |
Medical Research Council |
United Kingdom |
| MC_UU_12013/4 |
Medical Research Council |
United Kingdom |
| MC_UU_12013/5 |
Medical Research Council |
United Kingdom |
| WT088806 |
Wellcome Trust |
United Kingdom |
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| GENERAL NOTE |
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| KEYWORDS |
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| SUPPLEMENTARY MESH |
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| OTHER ID's |
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| OTHERID |
SOURCE |
| PMC4459389 [Available on 07/01/16] |
NLM |
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